Rosulip, pills 20mg 28pcs

Composition

Active ingredient:

each tablet contains 5 mg,10 mg,20 mg or 40 mg of rosuvastatin (in the form of, respectively: 5,34 / 10,68 / 21,36 / 42,72 mg of rosuvastatin zinc).

Auxiliary substances:

ludipress 65,16 / 130,32 / 260,64 / 521,28 mg [(lactose monohydrate (93%), povidone (3,5%), crospovidone (3,5%)], crospovidon 3,75/ 7,50/ 15,00/ 30,00 mg, magnesium stearate 0,75/ 1,50/ 3,00 / 6,00 mg; shell: Opadry II white 85F 18422 1,90 / 3,80 / 7,50 / 15,00 mg [polyvinyl alcohol (40%), titanium dioxide (25%), macrogol 3350 (20,2%), talc (14,8%)].

Round biconvex film-coated tablets, white or almost white in color, with the inscription E and the number 593 on one side of the tablet, odorless or almost odorless.

Pharmacological action

Pharmacotherapeutic group:

hypolipidemic agent-HMG-CoA reductase inhibitor.

ATX Code: C10AA07

PHARMACOLOGICAL PROPERTIES

Mechanism of action

Rosuvastatin is a selective, competitive inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, an enzyme that converts HMG-CoA to mevalonate, a cholesterol precursor. The main target of rosuvastatin action is the liver, where cholesterol synthesis and catabolism of low-density lipoproteins (LDL) are carried out.

Rosuvastatin increases the number of “hepatic” LDL receptors on the surface of liver cells, increasing the uptake and catabolism of LDL, which in turn leads to inhibition of the synthesis of very low-density lipoproteins (VLDL), thereby reducing the total amount of LDL and VLDL.

Pharmacodynamics

Rosuvastatin reduces elevated concentrations of cholesterol-LDL, total cholesterol and triglycerides (TG), increases the concentration of cholesterol-high density lipoprotein (HDL-C) and decreases concentrations of apolipoprotein b (APO B), cholesterol of lipoproteins of low density (XC-nalit), cholesterol-VLDL, TG-VLDL and increases the concentration of apolipoprotein A-I (APO A-I) (see tables 1 and 2) reduces the ratio of cholesterol-LDL/HDL-C, total cholesterol/HDL-C and HS-nalit/HDL-C ratio and APO b/APO A-I.

The therapeutic effect develops within one week after the start of treatment. After 2 weeks of therapy, the effectiveness reaches a level that is 90% of the maximum possible. The maximum therapeutic effect is usually achieved by the 4th week of therapy and is maintained with regular use of the drug.

Table 1. Dose-dependent effect in patients with primary hypercholesterolemia (type IIa and IIb according to the Fredrickson classification) (average adjusted percentage change compared to baseline).

Dosage	Number	of LDL-C patients	Total		Cholesterol HDL-C TG	HDL-C Non-HDL	Apo In	Apo A-I
Placebo	13-7-5			3-3-7-3				0
10 mg	17-52-36			14-10-48-42				4
20 mg	17-55-40			8-23-51-46				5
40 mg	18-63-46			10-28-60-54				0

Table 2. Dose-dependent effect in patients with hypertriglyceridemia (Fredrickson type IIb and IV) (mean percentage change from baseline).

Dosage	Number of patients	with TG	-LDL-C	Total	Cholesterol HDL-C-Non-HDL	C-VLDL	TG-VLDL
Placebo	26	1	5	1-3		2	2	6
10 mg	23-37-45-40				8-49-48-39
20 mg	27-37-31-34				22-43-49-40
40 mg	25-43-43-40				17-51-56-48

Clinical efficacy

Rosuvastatin is effective in adult patients with hypercholesterolemia with or without hypertriglyceridemia, regardless of race, gender, or age, including those with diabetes mellitus and familial hypercholesterolemia.

In 80% of patients with hypercholesterolemia type IIa and IIb according to the Fredrickson classification (the average initial concentration of LDL-C is about 4.8 mmol/l) against the background of taking the drug at a dose of 10 mg, the concentration of LDL-C reaches values of less than 3 mmol/l.

In patients with homozygous familial hypercholesterolemia, taking rosuvastatin at a dose of 20 mg and 40 mg, the average decrease in LDL-C concentration is 22%.

In patients with hypertriglyceridemia with an initial TG concentration of 273 to 817 mg / dl, receiving rosuvastatin at a dose of 5 mg to 40 mg once a day for 6 weeks, the concentration of TG in blood plasma significantly decreased (see table 2).

An additive effect is observed in combination with fenofibrate in relation to the concentration of TG and with nicotinic acid in lipid-lowering doses in relation to the concentration of HDL-C (see also the section “Special instructions”).

Pharmacokinetics

Absorption and distribution

The maximum plasma concentration of rosuvastatin (cmax) is reached approximately 5 hours after oral administration. Absolute bioavailability is approximately 20%.

Rosuvastatin is primarily metabolized by the liver, which is the main site of cholesterol synthesis and LDL-C metabolism. The volume of distribution₍vd) of rosuvastatin is approximately 134 liters. Approximately 90% of rosuvastatin binds to plasma proteins, mainly albumin.

Metabolism

It undergoes a limited metabolism (about 10%). Rosuvastatin is a non-core substrate for metabolism by cytochrome P450 isoenzymes. The main isoenzyme involved in the metabolism of rosuvastatin is CYP2C9. The isoenzymes CYP2C19, CYP3A4, and CYP2D6 are less involved in metabolism.

The main identified metabolites of rosuvastatin are N-desmethylrosuvastatin and lactone metabolites. N-desmethylrosuvastatin is approximately 50% less active than rosuvastatin, and the lactone metabolites are pharmacologically inactive. More than 90% of the pharmacological activity in inhibiting circulating HMG-CoA reductase is provided by rosuvastatin, the rest by its metabolites.

Deduction

Approximately 90% of the rosuvastatin dose is excreted unchanged through the intestine (including absorbed and unabsorbed rosuvastatin). The remaining part is excreted by the kidneys. The plasma half-life (T_1/2) is approximately 19 hours. T_1/2 does not change with increasing dose of the drug. The average geometric plasma clearance is approximately 50 l / h (coefficient of variation 21.7%). As in the case of other HMG-CoA reductase inhibitors, the process of” hepatic ” uptake of rosuvastatin involves a membrane transporter of cholesterol, which plays an important role in the hepatic elimination of rosuvastatin.

Linearity

Systemic exposure to rosuvastatin increases in proportion to the dose. Pharmacokinetic parameters do not change with daily use.

Special patient populations.

Age and gender

Gender and age do not have a clinically significant effect on the pharmacokinetics of rosuvastatin.

Ethnic groups

Pharmacokinetic studies have shown an approximately twofold increase in the median area under the concentration-time curve (AUC) and_cmax of rosuvastatin in patients of Asian descent (Japanese, Chinese, Filipino, Vietnamese, and Korean) compared to Europeans; in Indian patients, an increase in the median AUC and_cmax by 1.3 times was shown. Pharmacokinetic analysis revealed no clinically significant differences in pharmacokinetics between Europeans and Negroes.

Kidney failure

In patients with mild to moderate renal insufficiency, the plasma concentration of rosuvastatin or N-desmethylrosuvastatin does not change significantly. In patients with severe renal insufficiency (creatinine clearance (CC)) The plasma concentration of rosuvastatin in hemodialysis patients was approximately 50% higher than in healthy volunteers.

Liver failure

In patients with various stages of hepatic insufficiency (with a score of 7 or lower on the Child – Pugh scale), an increase in T_1/2 of rosuvastatin was not detected. Two patients with Child-Pugh scores of 8 and 9had at least a twofold increase in T 1/2. There is no experience of using rosuvastatin in patients with a score higher than 9 on the Child-Pugh scale.

Genetic polymorphism

HMG-CoA reductase inhibitors, including rosuvastatin, bind to the transport proteins OATP1B1 (an organic anion transport polypeptide involved in statin uptake by hepatocytes) and BCRP (efflux transporter). Carriers of the SLCO1B1 (OATP1B1) c. 521CC and ABCG2 (BCRP) c. 421AA genotypes showed a 1.6-and 2.4-fold increase in rosuvastatin exposure (AUC), respectively, compared to carriers of the SLCO1B1 c. 521TT and ABCG2 c. 421CC genotypes.

Indications

Primary hypercholesterolemia (type IIa according to the Fredrickson classification) or mixed hypercholesterolemia (type IIb) as a dietary supplement when diet and other non-drug treatments (for example, exercise, weight loss) are insufficient. Familial homozygous hypercholesterolemia as an adjunct to diet and other treatments aimed at reducing blood lipids (for example, LDL apheresis), as well as in cases where these methods are not effective enough. Hypertriglyceridemia (Fredrickson type IV) as a dietary supplement. To slow the progression of atherosclerosis as an adjunct to diet in patients, including those who are indicated for therapy to reduce the concentration of total cholesterol and LDL-C. Prevention of major cardiovascular complications (stroke, myocardial infarction, arterial revascularization) in adult patients without clinical signs of coronary heart disease (CHD), but with an increased risk of its development (age over 50 years for men and over 60 years for women, increased concentration of C-reactive protein (≥2 mg / l) in the presence of at least one of the additional risk factors, such as arterial hypertension, low HDL-C concentration, smoking, family history of early

Use during pregnancy and lactation

Rosulip is contraindicated during pregnancy and lactation (breastfeeding). If pregnancy is diagnosed during therapy, the drug should be discontinued immediately.

Women of reproductive age should use adequate methods of contraception. Since cholesterol and its biosynthetic products are important for fetal development, the potential risk of HMG-CoA reductase inhibition exceeds the benefit of the drug.

There are no data on the excretion of rosuvastatin in breast milk, so if it is necessary to use the drug during lactation, breastfeeding should be discontinued.

Contraindications

• hypersensitivity to rosuvastatin or any of the excipients of the drug;
• liver disease in the active phase, including a persistent increase in serum transaminases and any increase of transaminases in serum (>3 x upper limit of normal (ULN);
• severe impairment of renal function (QC < 30 ml/min);
• myopathy;
• concomitant use of cyclosporine;
• in women: pregnancy, breastfeeding, and lack of adequate methods of contraception in women with preserved reproductive function;
• patients predisposed to the development of myotoxicity complications;
• children up to age 18 years (due to lack of sufficient clinical data, the efficacy and safety not established, see section “Special instructions”);
• lactose intolerance, lactase deficiency or glucose-galactose malabsorption (product contains lactose).

With caution

Risk of developing myopathy/rhabdomyolysis – renal failure, hypothyroidism, personal or family history of inherited muscle diseases and previous history of muscle toxicity with other HMG-CoA reductase inhibitors or fibrates; excessive alcohol consumption; age over 65 years; conditions with increased plasma concentrations of rosuvastatin; race (Asian race); concomitant use with fibrates (see section “Pharmacokinetics”); a history of liver disease, sepsis; hypotension; extensive surgery, trauma, severe metabolic, endocrine, or electrolyte disturbances, or uncontrolled seizures.

Side effects

Side effects observed when taking the drug Rozulip®, usually expressed slightly and go away on their own. As with other HMG-CoA reductase inhibitors, the frequency of side effects is mainly dose-dependent.

The frequency of occurrence of undesirable effects is presented as follows:

often (> 1/100, > < 1/10); infrequently (> 1/1000, < 1/10); infrequently (>< 1/100); rarely (> 1/10000, < 1/100); rarely (>< 1/1000); very rarely (

The immune system

Rare: hypersensitivity reactions, including angioedema

Endocrine System

Common: Type 2 diabetes mellitus

Central nervous system (CNS)disorders 

Common: headache, dizziness

From the digestive tract

Often: constipation, nausea, abdominal pain

Rare: pancreatitis

From the side of the skin

Infrequently: pruritus, skin rash, urticaria

Musculoskeletal disorders

Common: myalgia

Rare: myopathy (including myositis), rhabdomyolysis

Other

Common: asthenic syndrome

From the urinary system

Patients treated with rosuvastatin may develop proteinuria. Changes in the amount of protein in the urine (from no or trace amounts to ++ or more) are observed in less than 1% of patients receiving 10-20 mg of the drug. A slight change in the amount of protein in the urine was observed when taking a dose of 20 mg. In most cases, proteinuria decreases or disappears during therapy and does not indicate the occurrence of acute or progressive existing kidney disease.

From the musculoskeletal system

The following effects on the musculoskeletal system have been reported with rosuvastatin at all doses and, in particular, with doses exceeding 20 mg: myalgia, myopathy (including myositis), in rare cases – rhabdomyolysis with or without acute renal failure.

A dose-dependent increase in creatine phosphokinase (CPK) activity is observed in a small number of patients taking rosuvastatin. In most cases, it was minor, asymptomatic, and temporary. In case of increased CPK activity (>5%^%x ULN), therapy should be suspended (see the section “Special instructions”).

From the liver

When using rosuvastatin, a dose-dependent increase in the activity of “hepatic” transaminases is observed in a small number of patients. In most cases, it is minor, asymptomatic, and temporary.

Laboratory parameters

When using rosuvastatin, the following changes in laboratory parameters were also observed: increased glucose concentration, bilirubin, gamma-glutamyltranspeptidase activity, alkaline phosphatase, and thyroid function disorders.

Post-marketing application

The following side effects have been reported in post-marketing use of rosuvastatin::

From the hematopoietic system

, the frequency is unknown: thrombocytopenia

From the digestive tract

Very rare: jaundice, hepatitis

Rare: increased activity of “hepatic” transaminases

Frequency unknown: diarrhea

From the musculoskeletal system

Very rare: arthralgia

Frequency unknown: immuno – mediated necrotizing myopathy

From the central nervous system

Very rare: Memory loss or decline

Frequency unknown: Peripheral neuropathy

Respiratory system disorders:

Frequency unknown: cough, shortness of breath

From the urinary system

Very rare: hematuria

Skin and subcutaneous fat

disorders Frequency unknown: Stevens-Johnson syndrome

From the side of the reproductive system and breast

, the frequency is unknown: gynecomastia

Other

Frequency unknown: peripheral edema

The following side effects have been reported with some statins::

depression, sleep disorders, including insomnia and “nightmarish” dreams, sexual dysfunction. Isolated cases of interstitial lung disease have been reported, especially with prolonged use of medications (see section “Special instructions”).

Interaction

Effect of other medications on rosuvastatin

Transport protein inhibitors: rosuvastatin binds to some transport proteins, in particular OATP1B1 and BCRP. Concomitant use of drugs that are inhibitors of these transport proteins may be accompanied by an increase in the concentration of rosuvastatin in plasma and an increased risk of developing myopathy (see Table 3 and sections “Dosage and use” and “Special Instructions”).

Cyclosporine: when rosuvastatin and cyclosporine were co-administered, the AUC of rosuvastatin was on average 7 times higher than that observed in healthy volunteers (see table 3). It does not affect the plasma concentration of cyclosporine. Rosulip® is contraindicated in patients taking cyclosporine (see section “Contraindications”).

HIV protease inhibitors: Although the exact mechanism of interaction is unknown, co-use of HIV protease inhibitors can lead to a significant increase in exposure to rosuvastatin (see table 3). A pharmacokinetic study of concomitant use of 20 mg rosuvastatin with a combination drug containing two HIV protease inhibitors (400 mg lopinavir/100 mg ritonavir) in healthy volunteers resulted in approximately a twofold or fivefold increase in AUC_(0-24)and_cmax of rosuvastatin, respectively. Therefore, simultaneous use of rosuvastatin and HIV protease inhibitors is not recommended (see sections “Dosage and use”, “Special instructions”, Table 3).

Gemfibrozil and other lipid-lowering agents: the combined use of rosuvastatin and gemfibrozil leads to a 2-fold increase in the_cmaxand AUC of rosuvastatin (see the section “Special instructions”). Based on the specific interaction data, no pharmacokinetically significant interaction with fenofibrate is expected, and a pharmacodynamic interaction is possible.

Gemfibrozil, fenofibrate, other fibrates and lipid-lowering doses of nicotinic acid increased the risk of myopathy when co-administered with HMG-CoA reductase inhibitors, possibly due to the fact that they can cause myopathy when used in monotherapy (see section “Special instructions”). When taking the drug simultaneously with gemfibrozil, fibrates, nicotinic acid in lipid-lowering doses (more than 1 g / day), patients are recommended an initial dose of 5 mg, taking a dose of 40 mg is contraindicated when co-administered with fibrates (see the sections “Contraindications”, “Method of use and doses”, “Special Instructions”).

Ezetimibe: concomitant use of 10 mg rosuvastatin and 10 mg ezetimibe was associated with an increase in rosuvastatin AUC in patients with hypercholesterolemia (see table 3). An increased risk of side effects can not be excluded due to the pharmacodynamic interaction between Rozulip® and ezetimibe.

Antacids: concomitant use of rosuvastatin and antacid suspensions containing magnesium and aluminum hydroxide leads to a decrease in the plasma concentration of rosuvastatin by approximately 50%. This effect is less pronounced if antacids are applied 2 hours after taking rosuvastatin. The clinical significance of this interaction has not been studied.

Erythromycin: concomitant use of rosuvastatin and erythromycin resulted in a 20% decrease _{in rosuvastatin AUC}and a 30% decrease in rosuvastatin cmax. This interaction may occur as a result of increased intestinal motility caused by taking erythromycin.

Cytochrome P450 isoenzymes: In vivo and in vitro studies have shown that rosuvastatin is neither an inhibitor nor an inducer of cytochrome P450 isoenzymes. In addition, rosuvastatin is a weak substrate for these isoenzymes. Therefore, rosuvastatin is not expected to interact with other drugs at the level of metabolism involving cytochrome P450 isoenzymes. There was no clinically significant interaction of rosuvastatin with fluconazole (an inhibitor of the CYP2C9 and CYP3A4 isoenzymes) and ketoconazole (an inhibitor of the CYP2A6 and CYP3A4 isoenzymes).

Fusidic acid: studies on the interaction of rosuvastatin and fusidic acid have not been conducted. As with other statins, there have been post-marketing reports of rhabdomyolysis with co-use of rosuvastatin and fusidic acid. Patients should be closely monitored. If necessary, it is possible to temporarily stop taking rosuvastatin.

Drug interactions that require dose adjustment of rosuvastatin (see table 3)

The dose of Rosulip® should be adjusted if it is necessary to use it together with drugs that increase exposure to rosuvastatin. You should read the instructions for use of these drugs before prescribing them together with rosuvastatin. If exposure is expected to increase by a factor of 2 or more, the initial dose of Rosulip®should be 5 mg once a day. The maximum daily dose of Rosuvastatin should also be adjusted so that the expected exposure to rosuvastatin does not exceed that for a dose of 40 mg taken without concomitant use of drugs that interact with rosuvastatin. For example, the maximum daily dose of Rosulip® when used concomitantly with gemfibrozil is 20 mg (1.9-fold increase in exposure), with ritonavir/atazanavir-10 mg (3.1-fold increase in exposure).

Table 3. Effect of concomitant therapy on exposure to rosuvastatin (AUC, data are given in descending order – – results of published clinical trials

Concomitant therapy regimen	Rosuvastatin treatment regimen	Changes in the AUC of rosuvastatin
Cyclosporine 75-200 mg 2 times a day, 6 months.	10 mg once a day,10 days	7.1 x increase
Atazanavir 300 mg / ritonavir 100 mg once daily,8 days	10 mg once	3.1 x increase
Simeprevir 152 mg once a day,7 days	10 mg once	2.8 x increase
Lopinavir 400 mg / ritonavir 100 mg twice daily,17 days	20 mg once daily,7 days	2.1 x increase
Clopidogrel 300 mg (loading dose), then 75 mg after 24 hours	20 mg once	2-fold increase
Gemfibrozil 600 mg 2 times daily,7 days	80 mg once	1.9 x increase
Eltrombopag 75 mg once a day,10 days	10 mg once	1.6-fold increase
Darunavir 600 mg / ritonavir 100 mg 2 times daily,7 days	10 mg 1 time daily,7 days	1.5 x increase
Tipranavir 500 mg / ritonavir 200 mg 2 times a day,11 days	10 mg once	1.4-fold increase
Dronedarone 400 mg 2 times a day.	No data available	1.4-fold increase
Itraconazole 200 mg once a day,5 days	10 mg or 80 mg once	1.4-fold increase
Ezetimibe 10 mg once daily,14 days	10 mg once daily,14 days	1.2 x increase
Fosamprenavir 700 mg / ritonavir 100 mg 2 times a day,8 days	10 mg once	No changes
Aleglitazar 0.3 mg,7 days	40 mg,7 days	No changes
Silymarin 140 mg 3 times a day,5 days	10 mg once	No changes
Fenofibrate 67 mg 3 times a day,7 days	10 mg,7 days	No changes
Rifampin 450 mg once a day,7 days	20 mg once	No changes
Ketoconazole 200 mg 2 times a day,7 days	80 mg once	No changes
Fluconazole 200 mg once a day,11 days	80 mg once	No changes
Erythromycin 500 mg 4 times a day,7 days	80 mg once	28% reduction
Baikalin 50 mg 3 times a day,14 days	20 mg once	47% reduction

Effect of rosuvastatin on other medications

Vitamin K antagonists: Starting rosuvastatin therapy or increasing the dose of the drug in patients receiving concomitant vitamin K antagonists (for example, warfarin) may lead to an increase in the International Normalized Ratio (INR). Discontinuation of rosuvastatin or a reduction in the dose of the drug may lead to a decrease in INR. In such cases, monitoring of INR is recommended.

Oral contraceptives / hormone replacement therapy: concomitant use of rosuvastatin and oral contraceptives increases the AUC of ethinyl estradiol and AUC of norgestrel by 26% and 34%, respectively. Such an increase in plasma concentration should be taken into account when selecting the dose of oral contraceptives. Pharmacokinetic data on the concomitant use of Rosulip® and hormone replacement therapy are not available, therefore, it is impossible to exclude a similar effect when using this combination. However, this combination was widely used during clinical trials and was well tolerated by patients.

Other medicinal products: no clinically significant interaction of rosuvastatin with digoxin is expected.

How to take, course of use and dosage

Inside, do not chew or crush the tablet, swallow whole, with water. The drug can be prescribed at any time of the day, regardless of food intake.

Before starting therapy with Rosulip®, the patient should begin to follow a standard hypocholesterolemic diet and continue to follow it during treatment. The dose of the drug should be selected individually, depending on the goals of therapy and the therapeutic response to treatment, taking into account current recommendations for the target concentration of lipids.

The recommended starting dose for patients starting to take the drug, or for patients transferred from taking other HMG-CoA reductase inhibitors, should be 5 or 10 mg of Rozulip® once a day. When choosing the initial dose, you should be guided by the individual concentration of cholesterol and take into account the possible risk of cardiovascular complications, as well as the potential risk of side effects. If necessary, the dose can be increased to a larger one after 4 weeks (see the section “Pharmacodynamics”).

Due to the possible development of side effects when taking a dose of 40 mg compared to lower doses of the drug (see section “Side effects”), an increase in the dose to 40 mg after an additional dose above the recommended initial dose for 4 weeks of therapy can only be carried out in patients with severe hypercholesterolemia and at high risk of cardiovascular complications (especially in patients with familial hypercholesterolemia), Especially careful monitoring of patients receiving the drug at a dose of 40 mg is recommended.

It is not recommended to prescribe a dose of 40 mg to patients who have not previously consulted a doctor.

After 2-4 weeks of therapy and/or when increasing the dose of Rosulip®, monitoring of lipid metabolism parameters is necessary (if necessary, dose adjustment is required).

Elderly patients

No dose adjustment is required.

Patients with renal insufficiency

No dose adjustment is required in patients with mild or moderate renal insufficiency. In patients with severe renal insufficiency (CC It is contraindicated to use the drug at a dose of 40 mg in patients with moderate renal impairment (creatinine clearance In patients with moderate renal impairment, an initial dose of 5 mg is recommended.

Patients with hepatic insufficiency

Rosulip® is contraindicated in patients with active liver disease (see sections “Contraindications”).

Special populations

Ethnic groups

When studying the pharmacokinetic parameters of rosuvastatin in patients belonging to different ethnic groups, an increase in the systemic concentration of rosuvastatin among Japanese and Chinese was noted (see the section “Special instructions”).

This fact should be taken into account when prescribing Rosulip® to these groups of patients. When prescribing doses of 10 and 20 mg, the recommended starting dose for patients of the Mongolian race is 5 mg. It is contraindicated to prescribe the drug at a dose of 40 mg to patients of the Mongolian race (see the section “Contraindications”).

Genetic polymorphism

Carriers of the SLCO1B1 (OATP1B1) c. 521CC and ABCG2 (BCRP) c. 421AA genotypes showed increased exposure (AUC) to rosuvastatin compared to carriers of the SLCO1B1 c. 521TT and ABCG2 c. 421CC genotypes. For patients with c. 521CC or c. 421AA genotypes, the recommended maximum dose of Rosulip® is 20 mg once daily (see sections “Pharmacokinetics”, ” Special instructions “and”Interaction with other drugs”).

Patients predisposed to myopathy

It is contraindicated to prescribe the drug at a dose of 40 mg to patients with factors that may indicate a predisposition to the development of myopathy (see the section “Contraindications”). When prescribing doses of 10 and 20 mg, the recommended initial dose for this group of patients is 5 mg (See the section “Contraindications”).

Concomitant therapy

Rosuvastatin binds to various transport proteins (in particular, c OATP1B1 and BCRP). Concomitant use of Rosuvastatin with medicinal products (such as cyclosporine, certain human immunodeficiency virus (HIV) protease inhibitors, including ritonavir and atazanavir, lopinavir and/or tipranavir) that increase the plasma concentration of rosuvastatin due to interaction with transport proteins may increase the risk of myopathy (including rhabdomyolysis) (see sections “Special instructions” and “Interaction with other medicinal products”). You should read the instructions for use of these drugs before prescribing them with Rosulip®, evaluate the possibility of prescribing alternative therapy or temporarily stopping taking Rosulip®. If the use of the above drugs is necessary, the benefit-risk ratio of concomitant therapy with Rosulip® should be evaluated and the possibility of reducing its dose should be considered (see the section “Interaction with other drugs”).

Overdose

With simultaneous use of several daily doses, the pharmacokinetic parameters of rosuvastatin do not change.

There is no specific treatment for rosuvastatin overdose. In case of overdose, it is recommended to carry out symptomatic and supportive therapy, measures aimed at maintaining the functions of vital organs and systems. Monitoring of liver function and CKD activity is necessary. The effectiveness of hemodialysis is unlikely.

Special instructions

Renal effects

Patients receiving high doses of rosuvastatin (mainly 40 mg) experienced tubular proteinuria, which in most cases was transient. Such proteinuria was not indicative of acute kidney disease or progressive kidney disease. In patients taking the drug at a dose of 40 mg, it is recommended to monitor the indicators of renal function during treatment.

From the musculoskeletal system

When using rosuvastatin in all dosages and, in particular, when taking doses of the drug exceeding 20 mg, the following effects on the musculoskeletal system have been reported: myalgia, myopathy, and in rare cases rhabdomyolysis.

Determination of CKD activity

Determination of CKD activity should not be performed after intense physical exertion or in the presence of other possible causes of increased CKD activity, which may lead to misinterpretation of the results obtained. If the initial CPK activity is significantly increased (>5 x ULN), a second measurement should be performed after 5-7 days. Therapy should not be initiated if repeated testing confirms baseline CPK activity (>5 x ULN).

Before starting therapy

When prescribing Rosulip®, as well as when prescribing other HMG-CoA reductase inhibitors, caution should be exercised in patients with existing risk factors for myopathy/rhabdomyolysis (see the section “With caution”), the risk-benefit ratio of therapy should be considered and clinical monitoring should be carried out.

During therapy

The patient should be informed of the need to immediately inform the doctor about cases of unexpected muscle pain, muscle weakness or spasms, especially in combination with malaise and fever. In such patients, CPK activity should be determined. Therapy should be discontinued if CKD activity is significantly increased (>5 x ULN) or if muscle symptoms are severe and cause daily discomfort (even if CKD activity is not increased >>5 x ULN). If symptoms disappear and CPK activity returns to normal, consideration should be given to re-prescribing Rosulip® or other HMG-CoA reductase inhibitors in smaller doses, with careful monitoring of the patient.

Routine monitoring of CPK activity in the absence of symptoms is impractical.

Very rare cases of immuno-mediated necrotizing myopathy with clinical manifestations of persistent weakness of the proximal muscles and increased activity of CPK in the blood serum were noted during treatment or upon discontinuation of statins, including rosuvastatin. Additional studies of the muscular and nervous system, serological studies, and immunosuppressive therapy may be required.

There were no signs of increased effects on skeletal muscle with rosuvastatin and concomitant therapy. However, an increase in myositis and myopathy has been reported in patients treated with other HMG-CoA reductase inhibitors in combination with fibrinic acid derivatives, including gemfibrozil, cyclosporine, nicotinic acid in lipid-lowering doses (more than 1 g/day), azole antifungal agents, HIV protease inhibitors, and macrolide antibiotics. Gemfibrozil increases the risk of myopathy when co-administered with certain HMG-CoA reductase inhibitors. Therefore, concomitant use of Rosulip and gemfibrozil is not recommended. The risk-benefit ratio should be carefully weighed when using Rosulip® together with fibrates or lipid-lowering doses of nicotinic acid. It is contraindicated to take the drug Rozulip® at a dose of 40 mg together with fibrates (see the sections “Interaction with other drugs”, “Contraindications”).

In 2-4 weeks after the start of treatment and/or when increasing the dose of Rosulip®, monitoring of lipid metabolism parameters is necessary (if necessary, dose adjustment is required).

The liver

It is recommended to determine liver function indicators before the start of therapy and 3 months after the start of therapy. Rosulip® should be discontinued or the dose of the drug should be reduced if the activity of “hepatic” transaminases in the blood serum is > 3 x ULN. >

In patients with hypercholesterolemia due to hypothyroidism or nephrotic syndrome, treatment of the underlying diseases should be performed before starting treatment with Rosulip®.

Special populations. Ethnic groups

In the course of pharmacokinetic studies among Chinese and Japanese patients, an increase in the systemic concentration of rosuvastatin was noted compared with the indicators obtained among European patients (see the sections “Dosage and use” and “Pharmacokinetics”).

HIV protease inhibitors

Concomitant use of the drug with HIV protease inhibitors is not recommended (see the section “Interaction with other drugs”).

Lactose

The drug should not be used in patients with lactase deficiency, galactose intolerance and glucose-galactose malabsorption.

Interstitial lung disease

Isolated cases of interstitial lung disease have been reported with the use of certain statins, especially for a long time. Symptoms of the disease may include shortness of breath, an unproductive cough, and poor overall health (weakness, weight loss, and fever). If interstitial lung disease is suspected, statin therapy should be discontinued.

Type 2 diabetes mellitus

In patients with a glucose concentration of 5.6 to 6.9 mmol / L, rosuvastatin therapy was associated with an increased risk of developing type 2 diabetes mellitus.

Application in pediatric practice

The efficacy and safety of Rosulip® in children under 18 years of age has not yet been established, so the use of this drug is contraindicated in patients of this age group.

INFLUENCE ON THE ABILITY TO DRIVE VEHICLES AND MECHANISMS

No studies have been conducted to study the effect of rosuvastatin on the ability to drive a vehicle and use mechanisms. However, based on the pharmacodynamic properties, rosuvastatin should not have such an effect. Caution should be exercised when driving vehicles or working with increased concentration and psychomotor response (dizziness may occur during therapy).

Form of production

Tablets

Storage conditions

Store at a temperature not exceeding 30 ° C. Keep the product out of the reach of children!

Shelf life

3 years

Active ingredient

Rosuvastatin

Conditions of release from pharmacies

By prescription

Dosage form

Tablets